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The Lustgarten Foundation has awarded Columbia University’s Herbert Irving Comprehensive Cancer Center (HICCC) a three-year grant, as part of its Translational Clinical Program, to test a new precision medicine approach to the treatment of metastatic pancreatic cancer.

“The prevailing model in personalized cancer treatment is to attack the DNA mutations that are believed to be driving an individual patient’s tumor,” says principal investigator Kenneth P. Olive, PhD , assistant professor of medicine and pathology & cell biology at HICCC. “While this approach has been astonishingly effective for a handful of rare cancers, we expect it will only work for a very small fraction of patients with the most common types of cancer.”

A research collaboration underway between Columbia’s Department of Systems Biology, the Broad Institute of MIT and Harvard, and Columbia University Medical Center (CUMC) is working to accelerate the discovery of new cancer drug combinations targeted at gastric and esophageal cancer. These tumors have not yet attracted prominent research focus and attention, and yet the general outcome for patients with these diseases is poor. According to the American Cancer Society, survival rates are only 20% at five years after diagnosis.

The newly formed research alliance between research teams at Columbia and at the Broad Institute came about thanks to a four-year gift by the Price Family Foundation, known for its philanthropic support of education, health, and biomedical research.

The PECASE is considered the United States’ highest award for young scientists and engineers, conferred annually at the White House at the recommendation of participating federal agencies. The award celebrates young researchers at the beginning of their independent research careers who show exceptional promise to lead at the frontiers of twenty-first century science and technology.

Clinical and molecular data are currently stored in many different databases using different semantics and different formats. A new project called DeepLink aims to develop a framework that would make it possible to compare and analyze data across platforms not originally intended to intersect. (Image courtesy of Nicholas Tatonetti.)

Medical doctors and basic biological scientists tend to speak about human health in different languages. Whereas doctors in the clinic focus on phenomena such as symptoms, drug effects, and treatment outcomes, basic scientists often concentrate on activity at the molecular and cellular levels such as genetic alterations, gene expression changes, or protein profiles. Although these various layers are all related physiologically, there is no standard terminology or framework for storing and organizing the different kinds of data that describe them, making it difficult for scientists to systematically integrate and analyze data across different biological scales. Being able to do so, many investigators now believe, could provide a more efficient and comprehensive way to understand and fight disease.

A new project recently launched by Nicholas Tatonetti (Assistant Professor in the Columbia University Departments of Systems Biology and Biomedical Informatics) along with co-principal investigators Chunhua Weng (Department of Biomedical Informatics) and Michel Dumontier (Stanford University), aims to bridge this divide. With the support of a $1.1 million grant from the National Center for Advancing Translational Science (NCATS) the scientists have begun to develop a tool they call DeepLink, a data translator that will integrate health-related findings at multiple scales.

As Dr. Tatonetti explains, “We want to close what we call the interoperability gap, a fundamental difference in the language and semantics used to describe the models and knowledge between the clinical and molecular domains. Our goal is to develop a scalable electronic architecture for integrating the enormous multiscale knowledge that is now available.”

The Columbia University Department of Systems Biology has been named one of four inaugural centers in the National Cancer Institute’s (NCI) new Cancer Systems Biology Consortium. This five-year grant will support the creation of the Center for Cancer Systems Therapeutics (CaST), a collaborative research center that will investigate the general principles and functional mechanisms that enable malignant tumors to grow, evade treatment, induce disease progression, and develop drug resistance. Using this knowledge, the Center aims to identify new cancer treatments that target master regulators of tumor homeostasis.

CaST will build on previous accomplishments in the Department of Systems Biology and its Center for Multiscale Analysis of Genomic and Cellular Networks (MAGNet), which developed several key systems biology methods for characterizing the complex molecular machinery underlying cancer. At the same time, however, the new center constitutes a step forward, as it aims to move beyond a static understanding of cancer biology toward a time-dependent framework that can account for the dynamic, ever-changing nature of the disease. This more nuanced understanding could eventually enable scientists to better predict how individual tumors will change over time and in response to treatment.

Each year, participants in the ISCB/RECOMB Conference on Regulatory and Systems Genomics select publications over the past year that they consider to have made the most significant contributions to the field. During the most recent conference, held in Philadelphia on November 15-18, 2015, the top 10 papers were announced. Among those selected were four involving Columbia University Department of Systems Biology investigators.

The International Society for Computational Biology has elected Professor Barry Honig to its 2016 ISCB Class of Fellows. The award recognizes distinguished ISCB members who shown excellence in research and/or service to the computational biology community. Dr. Honig’s award acknowledges his “seminal contributions to protein structure prediction and molecular electrostatics, and his more recent work on protein function prediction, protein-DNA recognition, and cell-cell adhesion.”

The International Society for Computational Biology is the largest professional society for scientists working in the fields of computational biology and bioinformatics. The 2016 Class of Fellows will be presented at its annual Intelligent Systems for Molecular Biology (ISMB) conference, to be held July 8-12, 2016 in Orlando, Florida.

Andrea Califano, the Clyde and Helen Wu Professor of Chemical Systems Biology and Chair of the Columbia University Department of Systems Biology, has been named a recipient of a National Cancer Institute Outstanding Investigator Award. The seven-year grant will support the development of systematic approaches for identifying the molecular factors that lead to cancer progression and to the emergence of drug resistance at the single-cell level.

The Transformative Research Award is a part of the NIH Common Fund’s High-Risk, High-Reward Research program, which provides critical funding to scientists it recognizes as being exceptionally creative and who propose particularly innovative approaches to solving key problems in biomedical research. The Transformative Research Award is designed to support projects that use methods and perspectives that are unconventional and untested, but show great potential to create or overturn fundamental paradigms.

Oliver Hobert, an interdisciplinary faculty member of the Department of Systems Biology, has received a Javits Neuroscience Investigator Award from the National Institute of Neurological Disorders and Stroke (NINDS). This prestigious grant provides long-term support for investigators who have demonstrated exceptional achievement throughout their careers. The award will enable the Hobert Lab to pursue a new project investigating sex-based differences in the regulation of neuronal identity.

Also a Professor of Biochemistry and Molecular Biophysics and an Investigator of the Howard Hughes Medical Institute, Dr. Hobert is known for his research using C. elegans to understand the molecular programs that control cell-type differentiation within the nervous system. C. elegans has become an invaluable model organism for studying the nervous system because it contains just over 300 neurons whose development has been studied in great detail.

The Columbia University Center for Topology of Cancer Evolution and Heterogeneity will combine mathematical approaches from topological data analysis with new single-cell experimental technologies to study cellular diversity in solid tumors. Image courtesy of Raul Rabadan.

The National Cancer Institute’s Physical Sciences in Oncology program has announced the creation of a new center for research and education based at Columbia University. The Center for Topology of Cancer Evolution and Heterogeneity will develop and utilize innovative mathematical and experimental techniques to explore how genetic diversity emerges in the cells that make up solid tumors. In this way it will address a key challenge facing cancer research in the age of precision medicine — how to identify the clonal variants within a tumor that are responsible for its growth, spread, and resistance to therapy. Ultimately, the strategies the Center develops could be used to identify more effective biomarkers of disease and new therapeutic strategies.

A grant from the Office of Naval Research will support the development of three foundational synthetic biology technologies for engineering the human gut microbiota.

Harris Wang, an assistant professor in the Columbia University Department of Systems Biology, has been selected for the Office of Naval Research 2015 Young Investigators Program. This highly selective program promotes the development of early-career academic scientists whose research shows exceptional promise and creativity. With the support of this award, Dr. Wang will extend his research in the field of synthetic biology to develop new technologies for engineering the gut microbiome, the ecosystem of bacteria that inhabit the human digestive system. These new methods, Wang anticipates, could provide new ways of designing communities of different microbial species and ultimately modulating interactions between the gut, the immune system, and the brain.

The Columbia University Department of Systems Biology congratulates Rodney Rothstein on his election to the National Academy of Sciences. The NAS is a private, non-profit society of distinguished scholars that provides independent, objective advice to the nation on matters related to science and technology. Scientists elected to the NAS are chosen by their peers in recognition of their distinguished and continuing achievements in original research.

Andrea Califano and Aris Floratos will lead an effort to reclassify tumors catalogued in TCGA according to their master regulators.

Andrea Califano and Aris Floratos, faculty members in the Columbia University Department of Systems Biology, have received a two-year, $624,236 subcontract to develop a new classification system of cancer subtypes. The agreement was awarded through a subcontract from Leidos Biomedical Research, Inc., which operates the Frederick National Laboratory for Cancer Research for the federal government.

By performing an integrative analysis of genomic data from the Cancer Genome Atlas (TCGA) and proteomic data from the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC), the researchers plan to recategorize tumors collected in TCGA based on the master regulator genes that determine their state. This is in contrast to other approaches based on expression of genes that reflect tissue lineage and proliferative processes. In addition, the team will link the genetics of each tumor sample to the specific master regulators that determine its state using a recently published novel algorithm (DIGGIT). Ultimately, the project aims to provide a more useful catalog of pan-cancer subtypes that could help to identify biomarkers and therapeutic targets for specific kinds of tumors, and ultimately provide a resource to guide the next generation of precision medicine.

“We have to reevaluate the way in which we organize tumors within subtypes, using both gene expression data and mutational data,” says Dr. Califano. “Right now the common approach is to classify tumor types based on rather generic genes that are differentially expressed between subtypes. But most of these genes play no role in actually driving the disease. We want to shift the emphasis and classify tumors based on the genes that truly regulate tumor state and survival.”

Harris Wang, an assistant professor in the Columbia University Department of Systems Biology and Department of Pathology and Cell Biology, has been selected to receive a 2015 Alfred P. Sloan Foundation Research Fellowship in computational and evolutionary molecular biology. This two-year, $50,000 grant will support work that combines methods from synthetic biology and computational biology to study how horizontal gene transfer contributes to microbial evolution.

Since 1955, the Sloan Research Fellowship program has supported outstanding early-career scientists in recognition of their achievements and their potential to make important contribution to their fields. This year’s fellows included 126 investigators, with 12 awardees in the field of computational and evolutionary molecular biology. Other disciplines represented in the awards include chemistry, computer science, economics, mathematics, neuroscience, ocean sciences, and physics.

Dana Pe'er has received the Pioneer Award for high-risk, high-reward research, and postdoctoral scientist Kyle Allison has won an Early Independence Award.

Two members of the Columbia University Department of Systems Biology have been named recipients of NIH Director’s Awards from the National Institutes of Health Common Fund.

Associate Professor Dana Pe’er is one of 10 winners of the 2014 NIH Director’s Pioneer Awards. The Pioneer Awards provide up to $2.5 million over 5 years to support exceptionally creative investigators who are pursuing “high risk, high reward” science that holds great potential to transform biomedical or behavioral research. The award will support an ambitious new project to develop the technological and computational methods necessary to create a comprehensive, high-resolution atlas of development for all cell types in the human body.

In addition, Kyle Allison, a postdoctoral scientist in the laboratory of Professor Saeed Tavazoie, has received the NIH Director’s Early Independence Award. (Dr. Tavazoie is also a past winner of the Pioneer Award.) This program enables outstanding young investigators who have recently completed their PhD’s to move rapidly into independent research positions. Dr. Allison is one of just 17 scientists to receive this award this year. In combination with the Department of Systems Biology Fellows program, this five-year, $1.25 million grant will allow him to open his own laboratory at Columbia and pursue independent research to investigate the problem of bacterial persistence. He is the second Department of Systems Biology investigator to receive the Early Independence Award, joining Assistant Professor Harris Wang in being recognized with this honor.

“Having four recipients of NIH Director’s Awards within the Department of Systems Biology — and particularly two in one year — is quite remarkable,” said Department Chair Andrea Califano. “I think it’s a testimony to the timeliness of the perspectives and tools that systems biology offers and to the high quality of research being conducted at Columbia. I look forward to the discoveries that will undoubtedly come from Dana’s and Kyle’s extremely exciting efforts.”

Dennis Vitkup, an associate professor in the Columbia University Department of Systems Biology and Department of Biomedical Informatics, has been awarded an R01 grant from the National Institute of General Medical Sciences (NIGMS) to develop a computational pipeline for predicting bacterial metabolic networks. Building on a framework called GLOBUS that was previously developed in his lab, the project will produce probabilistic annotations of metabolic networks for all of the major bacterial species that cause disease in humans. It will both offer a method that can be used to study metabolism in any species of bacteria and produce valuable information that will aid researchers who are looking for therapies against many of the world’s most deadly pathogens.

Congratulations to Brent Stockwell, one of 10 recipients of the 2014 Lenfest Distinguished Teaching Awards. Dr. Stockwell is an Associate Professor of Chemistry and Biological Sciences, and a member of the Columbia University Department of Systems Biology.

Established through a donation by trustee Gerry Lenfest (Law '58), the Lenfest Award recognizes faculty who are not only accomplished scholars but also exhibit excellence in instruction and mentorship, as well as university citizenship and professional involvement. Each recipient of the Lenfest Award receives a prize of $25,000 for a three-year period and is recognized at the Lenfest Award dinner.

Dana Pe’er, an associate professor in the Columbia University Department of Biological Sciences and Department of Systems Biology has been named the winner of the 2014 Overton Prize. Awarded by the International Society for Computational Biology (ISCB) since 2001, the Overton Prize recognizes one outstanding early- to mid-career scientist each year who has already made a significant contribution to the field of computational biology through research, education, service, or a combination of the three. The award recognizes Dr. Pe'er "for her cutting-edge research that applies computational methods to complex data to understand the organization of molecular networks in cells at a holistic systems level."

As the winner of the 2014 Overton Prize, Dr. Pe’er will receive the award and present a keynote address at the ISCB’s 22nd Annual International Conference on Intelligent Systems for Molecular Biology, which will be held in July 2014 in Boston.

In her research, Dr. Pe’er leads the development of computational methods for integrating large, diverse collections of high-throughput biological data, with the goal of understanding the structure and function of molecular networks. In recent work, she has focused on developing methods for interpreting data from single cells and characterizing heterogeneity in populations of cells with diverse phenotypes. She is also developing computational models for understanding the effects of epigenetic variation on regulatory network function and how these changes in regulatory networks lead to specific phenotypes in health and disease. These areas of investigation are particularly relevant within the field of cancer research, and the Pe’er lab’s findings and computational methods have offered new strategies for improving personalized medicine for cancer care.